Meet the researchers - Dr Claire Wells

Interview with Dr Claire Wells, who is a researcher in the Division of Cancer Studies at King's College London.

Her project funded by Pancreatic Cancer Research Fund aims to clarify the role of the PAK4 protein, which is believed to assist the spread of pancreatic cancer and which may prove to be a highly useful target for developing new drugs. She lives in the Midlands with her husband and two young daughters.

What started your career looking at cancer?During my undergraduate biology degree at UCL, my tutor, Dr. Joan Heaysman, showed us one of the first ever time lapse videos made of human cells crawling around. I was fascinated. We were shown normal cells and cancer cells, and I’ll never forget seeing cancer cells moving for the first time – they were so aggressive. I knew I wanted to continue working in cell biology.

For my PhD at Kings College, I chose to focus on cell motility, migration and invasion, and I learned everything I know about time lapse microscopy techniques. Nowadays every laboratory has a time lapse system, it’s a routine thing; but during my PhD it was a new and a very exciting advance. That fascination with cells continues to this day: there’s so much processing going on inside them, it’s so complex and there’s so much we still don’t understand.

Your work looks at a family of proteins called PAKs. What’s so special about PAKs?There are six members of the PAK family and they started to become interesting to the research community when it was identified that they might play different roles in regulating some processes within cells. This means they could be important in understanding what was happening in the development and spread of cancerous cells. They also have a 3-dimensional structure, which makes it easier to design new drugs to target them.

When I secured a postdoctoral position at UCL’s Ludwig Institute for Cancer Research, my supervisor, Anne Ridley, gave me a test tube of DNA with PAK4 in and told me to go and find out what it does and why. I only had one publication to my name at this point in my career, so it was a daunting task. But it was also incredibly exciting to have that freedom. We were working in the dark as very little was known about PAK4 at the time, and everything we thought would happen, didn’t, and vice versa. I’m still working on this protein – there’s so much to find out! Four research papers later, we have an idea of some of its roles, and understand the mechanisms by which it crawls around and we have theories on how it might help cancer cells to move around too, which we’re currently investigating. How did your work on PAK4 bring you to pancreatic cancer specifically?Three research papers came out in quick succession which showed that PAK4 was involved in pancreatic cancer, possibly helping to drive its highly aggressive and rapid invasion into other organs, so it was this that brought me to pancreatic cancer. I was shocked by the brutality and impact of this cancer, how quickly patients can deteriorate and how there are so few survivors. I applied for a Pancreatic Cancer Research Fund grant on the strength of my background in PAK4 because I want to find out exactly what role PAK4 plays, whether it’s a key driver, or more of a passenger. It’s important to know this, because pharmaceutical companies believe they can inhibit PAKs with certain types of drugs, so we need to know whether this is a good avenue for potential new therapies.

Do you get frustrated by how complex pancreatic cancer is?It’s frustrating that major advances in one cancer type don’t necessarily translate into progress in pancreatic. But you can’t allow yourself to get overwhelmed by the complexity; you just have to know that you’re contributing to the bigger picture. Cancer is a multifaceted process and it’s futile if researchers are working on their own. Collaboration is crucial, and the whole research community needs to work together to bring all the small pieces of new information together into the whole. This is why international research conferences are so important – we get the opportunity to discuss research and approaches with peers, and to inspire the younger generation of students and postdocs to generate their own ideas for new research projects.

Do you feel we’re close to making big advances with pancreatic cancer?As a whole community, I do believe we’re on the brink of huge advances. Looking back at the original cohort of chemotherapeutics, they were like big hammers and our approach has become much more sophisticated now. We’re finding potentially better targets – like PAKs. We’re drilling down into the disease using more detailed knowledge of more specific targets and using our understanding of different types of cancer to align treatments to the cancer type. We’re not using a ‘one size fits all’ approach anymore and the idea of personalised medicine is really gathering pace. If we find that PAK4’s role is key in some patients but not others, we can target PAK4 in those patients who will benefit. We’ve seen this happen with melanoma, where the BRAF gene mutation has been shown to figure prominently in many patients and drugs have been successfully designed to target this. This is exceptional science and we need to find BRAF equivalents with pancreatic so we can start to make a difference to survival.

You’re a supervisor of PhD students yourself now – how does this make you feel?Yes, I supervise several PhDs now, and one – Helen King – is funded by PCRF. I love working with these remarkably bright young researchers! I was lucky enough to have two incredible role models and supervisors in my early career and I feel the weight of responsibility to support my students through the dark times when their research isn’t working as planned and inspire them to publish original research, like I was in my early career. It’s a huge thrill for me to see them develop as scientists from my laboratory.

I hope that I can be a role model for young female researchers worried about whether it’s possible to combine being a mum with a career as a research scientist. It is possible to achieve a balance, but it takes dedication and support. I commute to London from the Midlands every day, and couldn’t do this without the support of my husband and parents who live close by. I do lots of work on the journey so I can spend lots of time with my girls.

What plans do you have for your future research direction?I made a strategic plan for myself recently to stay in pancreatic cancer research. This disease still drives me scientifically and there’s an awful lot to do. It’s getting tough as traditional funders like Cancer Research UK are pulling back from funding basic scientists like me. Thankfully, I work with clinicians like Hemant Kocher – who’s a co-applicant on my PCRF grant – to develop the more translational aspects of my research. Hemant teaches students to build 3D models for pancreatic cancer to test if PAKs are important for invasion. If we can get a robust model up and running it will make a big difference to advancing our knowledge of PAK4’s role in pancreatic cancer and potentially provide the pharmaceutical companies with a confirmed target for drug development.Hear Dr Wells describing the PCRF-funded project